著者

田所 作太郎 栗原 久

出版者

公益社団法人 日本薬理学会

雑誌

日本薬理学雑誌 (ISSN:00155691)

巻号頁・発行日

vol.95, no.5, pp.229-238, 1990 (Released:2007-02-20)

参考文献数

52

被引用文献数

24 25

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It has been well-known that a chronic abuse of amphetamines induces schizophrenia-like psychotic symptoms, namely amphetamine psychosis. When amphetamines are repeatedly administered to rodents, a reverse tolerance (behavioral sensitization) to the ambulationincreasing and/or stereotypy-producing effect is observed. The process of the reverse tolerance is affected by various factors. A clear reverse tolerance is produced when optimal doses of the drug (2 mg/kg, s.c. for mice, and 0.5 ?? 1 mg/kg, s.c., for rats) is administered at intervals of longer than 1 day rather than a shorter interval. Furthermore, the animal has to be put into a freely mobile situation during the presence of the acute drug effect. A cross reverse tolerance is observed between certain types of drugs that show an ambulation-increasing effect, although the potencies are different among the drugs. A reverse tolerance to the stereotypy (in particular sniffing and head-bobbing)producing effect is also observed when comparatively higher doses of methamphetamine are repeatedly administered. The process is qualitatively identical with the reverse tolerance to the ambulation-increasing effect produced by the repeated administration of comparatively smaller doses. The reverse-tolerance, once established, to both ambulation-increasing and stereotypy-producing effects is almost irreversible even with various treatments such as repeated post-treatment with antipsychotics. The characteristics of reverse tolerance to methamphetamine in animals might be closely correlated to the amphetamine psychosis in humans. It is also necessary to search for a method that effectively reduces the established reverse tolerance to amphetamines.